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ABSTRACT Aim We investigated the impact of proteinuria on the therapeutic effect before lenvatinib administration as second‐line treatment after atezolizumab‐bevacizumab. Methods We examined 64 patients who were administered lenvatinib as second‐line treatment after discontinuation of atezolizumab and bevacizumab. Proteinuria assessed before lenvatinib administration was considered severe if the qualitative value test (QV) was 3+ or the urine protein/creatinine ratio (UPCR) was ≥ 2.0 (group A, n = 13) and non‐severe if the UPCR was

A recent report on the detection of very-high-energy gamma rays from V4641 Sagittarii (V4641 Sgr) up to ≈0.8 PeV has made it the second confirmed “PeVatron” microquasar. Here we report on the observation of V4641 Sgr with X-Ray Imaging and Spectroscopy Mission (XRISM) in 2024 September. Thanks to the large field of view and low background, the CCD imager Xtend successfully detected for the first time X-ray extended emission around V4641 Sgr with a significance of ≳4.5 σ and >10 σ based on our imaging and spectral analysis, respectively. The spatial extent is estimated to have a radius of 7′ ± 3′ (13 ± 5 pc at a distance of 6.2 kpc) assuming a Gaussian-like radial distribution, which suggests that the particle acceleration site is within ~10 pc of the microquasar. If the X-ray morphology traces the diffusion of accelerated electrons, this spatial extent can be explained by either an enhanced magnetic field (∼80 μ G) or a suppressed diffusion coefficient (∼10 ^27 cm ^2 s ^−1 at 100 TeV). The integrated X-ray flux, (4–6) × 10 ^−12 erg s ^−1 cm ^−2 (2–10 keV), would require a magnetic field strength higher than the Galactic mean (≳8 μ G) if the diffuse X-ray emission originates from synchrotron radiation and the gamma-ray emission is predominantly hadronic. If the X-rays are of thermal origin, the measured extension, temperature, and plasma density can be explained by a jet with a luminosity of ∼2 × 10 ^39 erg s ^−1 , which is comparable to the Eddington luminosity of this system.

While the environment around Tycho's supernova remnant has long been believed to be close to homogeneous, the latest analysis of Chandra data has identified a substantial deceleration of the forward shock, which poses a major challenge to this picture. R. Kobashi et al. showed that the existence of dense molecular cloud (MC) surrounding a rarefied wind-like circumstellar matter (CSM) can explain this observational finding in terms of the shock-expansion dynamics, supporting the so-called single-degenerate scenario for the progenitor system. We here extend this work to study the nonthermal emission processes and investigate whether such an environment is consistent with the observed multiwavelength spectrum. While the simulated broadband spectrum based on the wind–MC environment is largely consistent with observations, we find that such an environment predicts a harder gamma-ray spectrum than observed due to the relatively low CSM density in the cavity interior of the MC. This difference can be at least partially attributed to the present 1D setup of the model, which does not account for the clumpy and multidimensional structure of the CSM. Our model provides predictions for the long-term evolution of the broadband spectrum, which can be used to further probe Tycho's surrounding environment in the future, a key to resolving the long-standing issue of Type Ia supernova progenitor channels.

Abstract Aim This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. Methods We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity‐score‐matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed‐effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow‐up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. Results Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were −2.41 ± 0.40 and −2.44 ± 0.42 at baseline, and −2.17 ± 0.56 and −2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p

The X-ray binary system Cygnus X-3 (4U 2030+40, V1521 Cyg) is luminous but enigmatic owing to the high intervening absorption. High-resolution X-ray spectroscopy uniquely probes the dynamics of the photoionized gas in the system. In this Letter, we report on an observation of Cyg X-3 with the XRISM/Resolve spectrometer, which provides unprecedented spectral resolution and sensitivity in the 2–10 keV band. We detect multiple kinematic and ionization components in absorption and emission whose superposition leads to complex line profiles, including strong P Cygni profiles on resonance lines. The prominent Fe xxv He α and Fe xxvi Ly α emission complexes are clearly resolved into their characteristic fine-structure transitions. Self-consistent photoionization modeling allows us to disentangle the absorption and emission components and measure the Doppler velocity of these components as a function of binary orbital phase. We find a significantly higher velocity amplitude for the emission lines than for the absorption lines. The absorption lines generally appear blueshifted by ∼−500–600 km s ^−1 . We show that the wind decomposes naturally into a relatively smooth and large-scale component, perhaps associated with the background wind itself, plus a turbulent, denser structure located close to the compact object in its orbit.

We report the first observational evidence for magnetic field amplification in the northeast/southwest (NE/SW) shells of supernova remnant SN 1006, one of the most promising sites of cosmic ray acceleration. In previous studies, the strength of magnetic fields in these shells was estimated to be B _SED ≃ 25 μ G from the spectral energy distribution, where the synchrotron emission from relativistic electrons accounted for radio to X-rays, along with the inverse Compton emission extending from the GeV to TeV energy bands. However, the analysis of broadband radio data, ranging from 1.37 to 100 GHz, indicated that the radio spectrum steepened from α _1 = 0.52 ± 0.02 to α _2 = 1.34 ± 0.21 by Δ α = 0.85 ± 0.21. This is naturally interpreted as a cooling break under a strong magnetic field of B _brk ≥ 2 mG. Moreover, the high-resolution MeerKAT image indicated that the width of the radio NE/SW shells was broader than that of the X-ray shell by a factor of only 3−20, as measured by Chandra. Such narrow radio shells can be naturally explained if the magnetic field responsible for the radio emissions is B _R ≥ 2 mG. Assuming that the magnetic field is locally enhanced by a factor of approximately a = 100 along the NE/SW shells, we argue that the filling factor, which is the volume ratio of such a magnetically enhanced region to that of the entire shell, must be as low as approximately k = 2.5 × 10 ^−5 .

We present an analysis of the first two XRISM/Resolve spectra of the well-known Seyfert-1.5 active galactic nucleus (AGN) in NGC 4151, obtained in 2023 December. Our work focuses on the nature of the narrow Fe K _α emission line at 6.4 keV, the strongest and most common X-ray line observed in AGN. The total line is found to consist of three components. Even the narrowest component of the line is resolved with evident Fe K _α _,1 (6.404 keV) and K _α _,2 (6.391 keV) contributions in a 2:1 flux ratio, fully consistent with neutral gas with negligible bulk velocity. Subject to the limitations of our models, the narrowest and intermediate-width components are consistent with emission from optically thin gas, suggesting that they arise in a disk atmosphere and/or wind. Modeling the three line components in terms of Keplerian broadening, they are readily associated with (1) the inner wall of the “torus,” (2) the innermost optical “broad-line region” (or “X-ray BLR”), and (3) a region with a radius of r ≃ 100 GM / c ^2 that may signal a warp in the accretion disk. Viable alternative explanations of the broadest component include a fast-wind component and/or scattering; however, we find evidence of variability in the narrow Fe K _α line complex on timescales consistent with small radii. The best-fit models are statistically superior to simple Voigt functions, but when fit with Voigt profiles the time-averaged lines are consistent with a projected velocity broadening of FWHM $\,=\,{1600}_{-200}^{+400}\,\mathrm{km}\,{{\rm{s}}}^{-1}$ . Overall, the resolution and sensitivity of XRISM show that the narrow Fe K line in AGN is an effective probe of all key parts of the accretion flow, as it is currently understood. We discuss the implications of these findings for our understanding of AGN accretion, future studies with XRISM, and X-ray-based black hole mass measurements.

Abstract Aim This study compared the efficacy and safety of atezolizumab and bevacizumab (Atez/Bev) in patients with viral and non‐viral infection in clinical settings. Methods We conducted the retrospective cohort study of 323 BCLC stage B or C hepatocellular carcinoma (HCC) patients with Child‐Pugh class A, and a performance status of 0 or 1 who started Atez/Bev from September 2020 to December 2021 at 22 institutions in Japan. Patients with viral infection was defined as those who were either serum anti‐HCV‐ Ab or HBs‐Ag‐positive, while patients with non‐viral infection was defined as those who were both serum anti‐HCV Ab‐ and HBs‐Ag‐negative. We constructed a propensity‐score‐matched cohort to minimize the risk of observable potential confounders. Results Propensity score matching produced 126 matched pairs for patients with viral versus non‐viral infection. After matching, the significant differences in baseline demographic features did not exist between the two groups. The objective response rate was 20.6% and 24.6% in viral‐ and non‐viral‐related HCC patients, respectively, without a significant difference (p = 0.55). The disease control rate was not also significantly different (68.3% vs 69.0%, p = 1.00). The median progression‐free survival was 7.0 months (95% confidence interval [CI] 6.0–9.6) and 6.2 months (95% CI 5.1–7.8) in patients with viral and non‐viral infection, and the 12‐month survival rates were 65.5% (95% CI 50.8–76.8) and 71.7% (95% CI 57.3–81.9) in those with viral and non‐viral infection, respectively, which were not significantly different (p = 0.33, p = 0.38). No significant difference in treatment‐related adverse events was found between the two groups. Conclusions Our etiology‐based study demonstrated that Atez/Bev showed good efficacy and safety for HCC patient with non‐viral infection as well as those with viral infection.

Abstract Background Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. Methods The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. Discussion This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. Trial registration This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019.

Abstract Aim This study investigated whether or not the hepatocellular carcinoma modified Gustave Roussy Immune Score (HCC‐GRIm‐Score) serves as a prognostic indicator for HCC patients treated with atezolizumab and bevacizumab (Atez/Bev). Methods A total of 405 HCC patients who received Atez/Bev from September 2020 to January 2022 at 22 different institutions were included in this retrospective study. The HCC‐GRIm score was based on the combination of the albumin level (

Abstract Aims This retrospective study compared the survival between elderly and non‐elderly patients. Methods A total of 5545 treatment‐naive patients with hepatocellular carcinoma (HCC) who visited 7 different hospitals from January 2000 to December 2018 were included. Patients ≥80 years old were defined as elderly patients. We divided the patients into three groups based on the timing of the initial treatment: Early, middle, and late periods defined as 2000 to 2005, 2006 to 2012, and 2013 to 2018, respectively. Results There were 132 (8.9%), 405 (17.5%), and 388 (22.2%) elderly patients in the early, middle, and late period, respectively, showing a significant increase over time (p

Abstract Background/Aim A comparison of therapeutic efficacy between atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib treatment given as first‐line therapy for unresectable hepatocellular carcinoma (u‐HCC) in regard to progression‐free survival (PFS) overall survival (OS) has not been reported. We aimed to elucidate which of those given as initial treatment for u‐HCC has greater prognostic impact on PFS and OS of affected patients, retrospectively. Materials/Methods From 2020 to January 2022, 251 u‐HCC (Child–Pugh A, ECOG PS 0/1, BCLC‐B/C) treated were enrolled (Atez/Bev‐group, n = 194; lenvatinib‐group, n = 57). PFS and OS were analyzed following adjustment based on inverse probability weighting (IPW). Results There was a greater number of patients with macro‐vascular invasion in Atez/Bev‐group (22.7% vs. 8.8%, p = 0.022). In lenvatinib‐group, the frequencies of appetite loss (38.6% vs. 19.6%, p = 0.002), hypothyroidism (21.1% vs. 6.7%, p = 0.004), hand foot skin reaction (19.3% vs. 1.0%, p

Abstract This study aimed to investigate the clinical characteristics of patients with unresectable hepatocellular carcinoma (HCC), who were eligible for sequential systemic therapy. We evaluated 365 patients with HCC who underwent systemic therapy after 2017. The overall survival (OS) was 13.7 months, 19.2 months, and 35.6 months in the first-line, second-line, and third-line or later therapy groups, respectively. Multivariate analysis revealed that the modified-albumin-bilirubin (m-ALBI) grade, macrovascular invasion, extrahepatic spread, discontinuation due to adverse events (AEs), and sequential therapy were independent factors for OS. At the end of each therapy, the ALBI score was significantly worse among patients with discontinuation due to AEs than among those without. The conversion rate to second-line and third-line therapy among patients with discontinuation due to AEs was significantly lower than that among patients without (30.4% vs. 69.2%, p

Abstract Aim The safety and efficacy of atezolizumab plus bevacizumab (Atez/Bev) in elderly patients with unresectable hepatocellular carcinoma (HCC) have not been sufficiently investigated. Methods A total of 317 patients with HCC treated with Atez/Bev were studied. We compared the survival and frequency of adverse events in elderly versus non‐elderly patients with HCC who were treated with Atez/Bev using an analysis of inverse probability weighting (IPW). Results Univariate analysis adjusted with IPW showed that being elderly is not associated with worse overall or progression‐free survival (hazard ratio [HR], 1.239; 95% confidence interval [CI], 0.640–2.399; p = 0.526 and HR, 1.256; 95% CI, 0.871–1.811; p = 0.223, respectively). Regarding treatment‐related adverse events, any grade of fatigue, proteinuria, decreased appetite, hypertension, and liver injury occurred in ≥10% of patients. There were no significant differences in treatment‐related adverse events between the elderly and non‐elderly groups. In a subgroup analysis of elderly patients aged 75–79, 80–84, or ≥ 85 years, there were no significant differences in cumulative overall or progression‐free survival among these age groups (p = 0.960 and 0.566, respectively). In addition, there were no significant differences in treatment‐related adverse events among these three age groups, except for proteinuria of any grade. In a subgroup analysis of patients treated with Atez/Bev as first‐line systemic therapy, there were no significant differences in cumulative overall or progression‐free survival between the elderly and non‐elderly groups (p = 0.728 and 0.805, respectively). Conclusions Atez/Bev can be used efficaciously and safely in spite of age in patients with unresectable HCC.

Among Type Ia supernova remnants (SNRs), Tycho’s SNR has been considered as a typical object from the viewpoints of its spectroscopic, morphological, and environmental properties. A recent reanalysis of Chandra data showed that its forward shock is experiencing a substantial deceleration since around 2007, which suggests recent shock interactions with a dense medium as a consequence of a cavity-wall environment inside a molecular cloud. Such a nonuniform environment can be linked back to the nature and activities of its progenitor. In this study, we perform hydrodynamic simulations to characterize Tycho’s cavity-wall environment using the latest multiepoch proper motion measurements of the forward shock. A range of parameters for the environment is explored in the hydrodynamic models to fit with the observational data for each azimuthal region. Our results show that a wind-like cavity with ρ ( r ) ∝ r ^−2 reconciles with the latest data better than a uniform medium with a constant density. In addition, our best-fit model favors an anisotropic wind with an azimuthally varying wind parameter. The overall result indicates a mass-loss rate which is unusually high for the conventional single-degenerate explosion scenario.

While various methods have been proposed to disentangle the progenitor system for Type Ia supernovae, their origin is still unclear. A circumstellar environment is key to distinguishing between the double-degenerate and single-degenerate (SD) scenarios since a dense wind cavity is expected only in the case of the SD system. We perform spatially resolved X-ray spectroscopy of Tycho’s supernova remnant (SNR) with XMM-Newton and reveal the three-dimensional velocity structure of the expanding shock-heated ejecta measured from Doppler-broadened lines of intermediate-mass elements. Obtained velocity profiles are fairly consistent with those expected from a uniformly expanding ejecta model near the center, whereas we discover a rapid deceleration (∼4000 to ∼1000 km s ^−1 ) near the edge of the remnant in almost every direction. The result strongly supports the presence of a dense wall entirely surrounding the remnant, which is confirmed also by our hydrodynamical simulation. We thus conclude that Tycho’s SNR is likely of SD origin. Our new method will be useful for understanding progenitor systems of Type Ia SNRs in the era of high-angular/energy-resolution X-ray astronomy with microcalorimeters.

IRAS 00500+6713 is a hypothesized remnant of a Type Iax supernova SN 1181. Multiwavelength observations have revealed its complicated morphology; a dusty infrared ring is sandwiched by the inner and outer X-ray nebulae. We analyze the archival X-ray data taken by XMM-Newton and Chandra X-ray Observatory to constrain the angular radius, mass, and metal abundance of the X-ray nebulae, and construct a theoretical model describing the dynamical evolution of IRAS 00500+6713, including the effects of the interaction between the SN ejecta and the intense wind enriched with carbon-burning ashes from the central white dwarf (WD) J005311. We show that the inner X-ray nebula corresponds to the wind termination shock while the outer X-ray nebula to the shocked interface between the SN ejecta and the interstellar matter. The observed X-ray properties can be explained by our model with an ejecta kinetic energy of E _ej = (0.77–1.1) × 10 ^48 erg, an ejecta mass of M _ej = 0.18–0.53 M _⊙ , if the currently observed wind from WD J005311 started to blow t _w ≳ 810 yr after the explosion, i.e., approximately after 1990 CE. The inferred SN properties are compatible with those of Type Iax SNe and the timing of the wind launch may correspond to the Kelvin–Helmholtz contraction of the oxygen–neon core of WD J005311 that triggered a surface carbon burning. Our analysis supports that IRAS 00500+6713 is the remnant of SN Iax 1181 produced by a double degenerate merger of oxygen–neon and carbon–oxygen WDs, and WD J005311 is the surviving merger product.

HESS J1641−463 is an unidentified gamma-ray source with a hard TeV gamma-ray spectrum, and thus it has been proposed to be a possible candidate for a cosmic-ray (CR) accelerator up to PeV energies (a PeVatron candidate). The source spatially coincides with the radio supernova remnant G338.5+0.1 but has not yet been fully explored in the X-ray band. We analyzed newly taken NuSTAR data, pointing at HESS J1641−463, with 82 ks effective exposure time. There is no apparent X-ray counterpart of HESS J1641−463, while nearby stellar cluster, Mercer 81, and stray-light X-rays are detected. Combined with the archival Chandra data, partially covering the source, we derived an upper limit of ∼6 × 10 ^−13 erg cm ^−2 s ^−1 in 2–10 keV (∼3 × 10 ^−13 erg cm ^−2 s ^−1 in 10–20 keV). If the gamma-ray emission is originated from the decay of π ^0 mesons produced in interactions between CR protons and ambient materials, secondary electrons in the proton–proton interactions can potentially emit synchrotron photons in the X-ray band, which can be tested by our X-ray observations. Although the obtained X-ray upper limits cannot place a constraint on the primary proton spectrum, it will be possible with a future hard X-ray mission.

Abstract We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2–22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495–2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR (p

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e., the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (≥30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (p < 0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Abstract Background The fixation strength of bone screws depends on bone mineral density (BMD), so it is important to evaluate bone strength at fracture sites. Few studies have investigated BMD in the pelvis. The aims of this study were to measure the regional Hounsfield unit (HU) values in the cancellous bone of the acetabulum and pelvic ring and to compare these values between young and older patients. Methods This study enrolled young patients with high-energy trauma (aged 20–44 years; young group) and older patients with low-energy trauma (aged 65–89 years; older group). Patients without pelvic computed tomography (CT) scans, those with pelvic bone implants, and those who died were excluded. The HU values on the contralateral (non-fractured) side of the pelvis were measured on CT scans. The CT data were divided into 7 areas: the pubic bone, the anterior and posterior walls and roof of the acetabulum, the ischial tuberosity, the body of the ilium, and the third lumbar vertebra. The HU values in each area were compared between the young and older groups. Results Sixty-one young patients and 154 older patients were included in the study. The highest HU value was in the roof of the acetabulum regardless of age and sex. HU values were significantly higher in the ischial tuberosity and body of the ilium and lower in the pubic bone and anterior wall. The HU values in all pelvic areas were significantly lower in the older group than in the young group, especially in the anterior area. Conclusions HU values in the 6 pelvic areas were not uniform and were strongly related to load distribution. The HU distribution and age-related differences could explain the characteristic causes and patterns of acetabular fractures in the older and may help in surgical treatment.

Abstract Background Several retrospective studies have reported spine–femur discordance in bone mineral density (BMD) values. However, the average age of individuals in these studies was the mid-50s, which is younger than the typical age of individuals requiring treatment for primary osteoporosis. Therefore, we aimed to investigate factors associated with discordance in the percentage of young adult mean (YAM) between the lumbar spine and femoral neck in the elderly population. Methods We evaluated 4549 dual-energy X-ray absorptiometry (DXA) measurements obtained from 2161 patients (269 men and 1892 women) between January 2014 and December 2017 at our hospital. For individuals with more than one eligible set of measurements, the first record was used. We investigated each patient’s age, sex, body mass index, current smoking status, alcohol consumption, use of steroids, presence of diabetes mellitus, and presence of rheumatoid arthritis. Results The mean age of the patients was 76.4 ± 8.9 years. Older age (p 10% of YAM. Furthermore, the frequency of spine–femur discordance was higher in men and in patients with diabetes mellitus, suggesting that the percentage of YAM at the lumbar spine may not be reliable for diagnosis of osteoporosis in patients with these factors.

Abstract Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Background: Cartilage degradation progresses rapidly following medial meniscus posterior root tear (MMPRT). Unicompartmental knee arthroplasty (UKA) has been performed for medial compartmental osteoarthritis following MMPRT. We evaluated the clinical and radiographic outcomes of UKA for medial compartmental osteoarthritis after an untreated MMPRT. Methods: Twenty-one patients who underwent UKA for isolated medial compartment osteoarthritis following MMPRT were retrospectively investigated. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score and knee range of motion. The posterior tibial slope and tibial component inclination were evaluated using plain radiographs. Results: The mean follow-up periods were 25.5 ± 13.8 months. Clinical outcomes improved significantly postoperatively. The mean postoperative knee extension angle was −1.1° ± 2.1°, and the knee flexion angle was 134.3° ± 4.9°. The posterior tibial slope angle decreased from 9.0° ± 2.0° preoperatively to 5.4° ± 1.8° postoperatively, and postoperative tibial component inclination at the final follow-up was 2.9° ± 1.1° varus. No aseptic loosening or deep infections were observed. Conclusion: UKA significantly improved clinical outcomes and could be a viable surgical option for treating isolated medial compartmental osteoarthritis accompanied by untreated MMPRT.

Abstract Background and Aim Spleen stiffness measurement (SSM) is useful for assessing portal hypertension. It is unclear whether SSM values are appropriate because vibration‐controlled transient elastography (VCTE) does not generate B‐mode images. This study aimed to confirm whether the controlled attenuation parameter (CAP) measured in the spleen can predict the accuracy of SSM. Methods This retrospective study enrolled 349 patients who underwent SSM using VCTE from January 2012 to December 2020. Consecutive patients were classified into the pilot set (SSM and hepatic venous pressure gradient [HVPG] were measured) and the validation set (SSM was measured without HVPG). In the pilot set, scatter plots with a nonparametric contour line were created. Logistic regression analysis was performed to predict outliers outside the 50% contour line. Results The values of CAP could distinguish the outliers in scatter plots between the HPVG and SSM in both univariate and multivariate analyses (cutoff, 118 dB/m). The correlation of SSM with HVPG (r = 0.718; P 118 dB/m) group (r = 0.330; P

Background/Aim: There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev. Materials/Methods: From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others=81:33:40:75; Child-Pugh A, 212 (92.6%); mALBI grade 1:2a:2b=79:60:90; BCLC 0:A:B:C =1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated. Results: Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95%CI 1.264-2.702, P=0.002), modified albumin-bilirubin (mALBI) grade (≥2a) (HR 1.563, 95%CI 1.035-2.359, P=0.034), and MVL (HR 1.479, 95%CI 1.020-2.144, P=0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95%CI 1.856-6.844, P

Abstract It was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P

Hepatocellular carcinoma has been considered to disseminate through the tumor blood drainage area. To improve curation rates, treatment should cover this area as it may contain satellite lesions. This retrospective study aimed to investigate whether radiofrequency ablation (RFA) completely covering the blood drainage area can improve the overall and disease‐free survival. We enrolled 526 patients who underwent computed tomography during hepatic arteriography following RFA from April 2001 to May 2019. Patients were categorized into a covered group in which the blood drainage area was completely covered by RFA and a noncovered group in which coverage was incomplete. The primary endpoint was the overall survival rate; secondary outcomes included disease‐free survival rate, distant intrahepatic and local recurrence rate, and changes in the Child‐Pugh score. There were no significant differences in baseline characteristics between the two groups. Cumulative overall survival rates were significantly higher in the covered group than in the noncovered group (hazard ratio, 0.63; 95% confidence interval, 0.48‐0.84; P = 0.002). On multivariate Cox proportional hazard model analysis, age

A Ni(OH)2 surface was fluorinated at 25 °C using F2 gas for 1 h under absolute pressure of 6.67 kPa. Some fluorides and oxyfluorides were detected only on the Ni(OH)2 particle surface, although most Ni(OH)2 remained inside of the particles. Fluorine-introduced NiO (NiO(F)) was obtained by heating the surface-fluorinated Ni(OH)2. After sintering at 750 °C for 6 h, the NiO(F) crystal size and surface area were, respectively, 0.6 times smaller and 4.7 times larger than those of NiO obtained from untreated Ni(OH)2. LiNiO2 samples were prepared via reaction between NiO(F) and Li2CO3 at 700 °C for 20 h and 30 h, respectively (LiNiO2 (20 h, F) and LiNiO2 (30 h, F)). The density of LiNiO2 (30 h, F) was 4.697, which was larger than the 4.556 of LiNiO2 prepared from NiO and Li2CO3 under the same conditions. The discharge capacity of LiNiO2 (30 h, F) was 202 mAh g−1, whereas the LiNiO2 prepared under the same condition from NiO and Li2CO3 was 172 mAh g−1. The discharge capacity of LiNiO2 as a cathode of LIB might be improved by introducing fluorine to its preparation process between NiO and Li2CO3.

Abstract Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.

A 69-year-old man presented with a pulmonary opacity at a regular medical check-up. He had been exposed to asbestos in a chemical fiber manufacturing setting. Result of positron emission tomography with computed tomography (CT) revealed fluorodeoxyglucose accumulations along the right pleura in areas with multiple nodules and irregular pleural thickening. On the basis of analysis of a CT-guided needle biopsy result, he had been diagnosed with having epithelioid malignant pleural mesothelioma. He received neoadjuvant chemotherapy, and subsequently, a pleurectomy and decortication. After 6 months, malignant pleural mesothelioma recurred with multiple tumors in the pleural cavity. Nivolumab was administered as salvage immunotherapy. A CT scan result revealed marked tumor reduction; however, his platelet count was low (8000/μL), and he was diagnosed with having nivolumab-induced immune thrombocytopenia. Oral prednisone and thrombopoietin receptor agonist were delivered, and the platelet count improved; therefore, a sustained cycle of nivolumab was resumed. This case revealed that nivolumab could be readministered for continued antitumor effects, with careful management of immune-related adverse events.

Abstract Background Platelet-rich plasma (PRP) is often used to improve surface biocompatibility. We previously found that platelets rapidly adhere to plain commercially pure titanium (cp-Ti) plates in the absence, but not in the presence, of plasma proteins. To further expand on these findings, in the present study, we switched titanium plates from a plain surface to a rough surface that is blasted with calcium phosphate (CaP) powder and then examined platelet adhesion and activation. Methods Elemental distribution in CaP-blasted cp-Ti plates was analyzed using energy-dispersive X-ray spectroscopy. PRP samples prepared from anticoagulated blood samples of six healthy, non-smoking adult male donors were loaded on CaP-blasted cp-Ti plates for 1 h and fixed for examination of platelet morphology and visualization of PDGF-B and platelet surface markers (CD62P, CD63) using scanning electron microscopy and fluorescence microscopy. Plain SUS316L stainless steel plates used in injection needles were also examined for comparison. Results Significant amounts of calcium and phosphate were detected on the CaP-blasted cp-Ti surface. Platelets rapidly adhered to this surface, leading to higher activation. Platelets also adhered to the plain stainless surface; however, the levels of adhesion and activation were much lower than those observed on the CaP-blasted cp-Ti plate. Conclusions The CaP-blasted cp-Ti surface efficiently entraps and activates platelets. Biomolecules released from the activated platelets could be retained by the fibrin matrix on the surface to facilitate regeneration of the surrounding tissues. Thus, PRP immersion could not only eliminate surface air bubbles but also improve the biocompatibility of the implant surface.

A 55-year-old man experienced nausea and vomiting after brushing his teeth. He experienced back pain after this episode and visited our emergency department. Chest computed tomography (CT) images revealed moderate pleural fluid accumulation and mild left pneumothorax. Thoracentesis showed black pleural effusion. Thoracic drainage included food debris with black pleural effusion, and gastroscopy revealed food debris and perforation of the lower esophagus. Esophageal perforation was surgically repaired using omental implantation and pleuroclysis. Given the high mortality rate associated with black pleural effusion, prompt diagnostic procedures and corresponding management are essential.

Stellar winds blown out from massive stars (≳10 M _⊙ ) contain precious information on the progenitor itself, and in this context the most important elements are carbon (C), nitrogen (N), and oxygen (O), which are produced by the CNO cycle in the H-burning layer. Although their X-ray fluorescence lines are expected to be detected in swept-up shock-heated circumstellar materials in supernova remnants, those of C and N have been particularly difficult to detect so far. Here, we present high-resolution spectroscopy of the young magnetar-hosting supernova remnant RCW 103 with the Reflection Grating Spectrometer on board XMM-Newton and report on the detection of the N vii Ly α (0.50 keV) line for the first time. By comparing the obtained abundance ratio of N to O (N/O = 3.8 ± 0.1) with various stellar evolution models, we show that the progenitor of RCW 103 is likely to have a low mass (10–12 M _⊙ ) and medium rotation velocity (≲100 km s ^−1 ). The results also rule out the possibility of dynamo effects in massive (≥35 M _⊙ ) stars as a mechanism for forming the associated magnetar 1E 161348−5055. Our method is useful for estimating various progenitor parameters for future missions with microcalorimeters such as XRISM and Athena.

The kinematics of shocks, ejecta knots, and the compact remnant of a supernova remnant give insights into the nature of the progenitor and the surrounding environment. We report on a measurement of the proper motion of X-ray knots and rims of the magnetar-hosting supernova remnant RCW 103. Chandra data obtained in three epochs, 1999, 2010, and 2016, are used. We find a global deceleration of 12 knots and rims in both northern and southern regions within the last ∼24 yr, even though the age of the remnant is thought to be greater than 2 kyr. Some of them even changed their directions of motion from outward (∼1000 km s ^−1 ) to inward (∼−2000 km s ^−1 ). Our findings can be explained by a collision with a high-density medium at both the northern and southern edges of the remnant, although the remnant may still be expanding in the windblown cavity. The proper motion of the associated magnetar 1E 161348−5055 is possibly detected with a velocity of ≈500 km s ^−1 .

A 70-year-old woman underwent right upper lobectomy for adenocarcinoma of the lung (pT1bN2M0 stage IIIA). Five years after the surgery, lymph node recurrence was detected. Gefitinib was administered because epidermal growth factor (EGFR) exon 19 deletion mutation was detected in the previously resected surgical specimen. After a treatment of first-generation EGFR tyrosine kinase inhibitors, an FDG-PET/CT scan demonstrated abnormal FDG uptake in the pleura indicating pleural dissemination. Pleurocentesis revealed tumor cells in the pleural fluid; however, EGFR mutation testing failed due to inadequate tumor cellularity. Thoracoscopy under local anesthesia revealed multiple nodules on the parietal pleura. A biopsy specimen confirmed the diagnosis of lung adenocarcinoma with pleural dissemination and revealed EGFR exon 20-T790M mutation.

Abstract Background It has been reported that the microporous structure of calcium phosphate (CaP) ceramics is important to osteoconduction. Bone morphogenetic protein-2 (BMP-2) has been shown to be a promising alternative to bone grafting and a therapeutic agent promoting bone regeneration when delivered locally. The aim of this study was to evaluate the effects of micro-porosity within beta-tricalcium phosphate (β-TCP) cylinders and local BMP-2 administration on β-TCP resorption and new bone formation. Methods Bilateral cylindrical bone defects were created in rabbit distal femora, and the defects were filled with β-TCP. Rabbits were divided into 3 groups; defects were filled with a β-TCP cylinder with a total of approximately 60% porosity (Group A: 13.4% micro- and 46.9% macropore, Group B: 38.5% micro- and 20.3% macropore, Group C: the same micro- and macro-porosity as in group B supplemented with BMP-2). Rabbits were sacrificed 4, 8, 12, and 24 weeks postoperatively. Results The number of TRAP-positive cells and new bone formation in group B were significantly greater than those in group A at every period. The amount of residual β-TCP in group C was less than that in group B at all time periods, resulting in significantly more new bone formation in group C at 8 and 12 weeks. The number of TRAP-positive cells in group C was maximum at 4 weeks. Conclusions These results suggest that the amount of submicron microporous structure and local BMP-2 administration accelerated both osteoclastic resorption of β-TCP and new bone formation, probably through a coupling-like phenomenon between resorption and new bone formation.

BackgroundHepatic venous pressure gradient (HVPG) is the gold standard index for evaluating portal hypertension; however, measuring HVPG is invasive. Although transient elastography (TE) is the most common procedure for evaluating organ stiffness, accurate measurement of spleen stiffness (SS) is difficult. We developed a device to demonstrate the diagnostic precision of TE and suggest this technique as a valuable new method to measure SS.MethodsOf 292 consecutive patients enrolled in this single-centre, translational, cross-sectional study from June through September in 2019, 200 underwent SS measurement (SSM) using an M probe (training set, n = 130; inspection set, n = 70). We performed TE with B-mode imaging using an ultrasound-fusion method, printed new devices with a three-dimensional printer, and attached the magnetic position sensor to the convex and M probes. We evaluated the diagnostic precision of TE to evaluate the risk of esophagogastric varices (EGVs).ResultsThe median spleen volume was 245 mL (range, 64-1,720 mL), and it took 2 minutes to acquire a B-mode image using the ultrasound-fusion method. The median success rates of TE were 83.3% and 57.6% in patients with and without the new device, respectively (pConclusionsThe SS can be precisely measured using this new device with TE and ultrasound-fusion method. Similarly, we can estimate the bleeding risk due to EGV using this method.

This report describes a novel arthroscopic technique for the treatment of anterior cruciate ligament (ACL) tibial eminence avulsion fractures. A 16-year-old boy who was diagnosed with a left ACL tibial eminence avulsion fracture was treated by arthroscopic fixation. Two bone tunnels were created from the anterior tibial cortex into the fracture bed, and a strong suture passed through the ACL just above its insertion was pulled out through them for reduction and fixation. A retrograde cannulated screw fixation was added for stronger fixation. Weight-bearing and range of motion exercises were started immediately after surgery. Radiographically, bone union was obtained 6 months postoperatively. During second-look arthroscopy (24 months postoperatively), there was no loss of reduction and no subsequent meniscal or cartilage injuries. At that point, the Lysholm score was 95, and the International Knee Documentation Committee score was 96.

Abstract Background Platelet-rich plasma (PRP) is widely used in regenerative dentistry and other medical fields. However, its effectiveness has often been questioned. For better evaluation, the quality of individual PRP preparations should be assured prior to use. We proposed a spectrophotometric method for determination of platelet counts and validated its applicability using two types of PRP preparations. Methods Blood samples were obtained from healthy male volunteers and pure PRP (P-PRP) and leukocytes-rich PRP (L-PRP) were prepared using the double-spin method. In serial dilutions, platelet counts in P-PRP and L-PRP were determined using an automated hematology analyzer and a compact spectrophotometer. For validation, P-PRP and L-PRP independently prepared by three well-trained operators were used for comparison of the calculated and measured platelet counts. Results In the two types of PRP samples evaluated, platelet counts were almost equal and greater amount of both white blood cells (WBCs) and red blood cells (RBCs) were included in L-PRP preparations. The calibration curve obtained from serially diluted P-PRP showed a strong correlation (R 2 = 0.995), whereas that of L-PRP was relatively weaker (R 2 = 0.975). In validation testing, the scatter plot of the calculated platelet counts versus the measured values showed a strong correlation in P-PRP (R 2 = 0.671), whereas that of L-PRP showed a much weaker correlation (R 2 = 0.0605). Conclusions This method can precisely determine platelet counts in PRP preparations when the inclusion of WBCs or RBCs is minimized. Therefore, we recommend that clinicians use this method for quality assurance of individual PRP preparations.

Abstract Background Ovarian serous borderline tumor/atypical proliferative serous tumor (SBT/APST) is characterized by presenting at an early stage and much longer survival than high-grade serous carcinoma. Given that the prognosis of ovarian SBT/APST with no invasive features is excellent, remote relapse after surgery can pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is an extremely rare initial presentation of recurrence in patients whose primary tumor was confined to the ovaries. Case presentation A 55-year-old Japanese woman who had undergone surgery for a right ovarian tumor 13 years previously presented with right-lateral chest pain and neurologic abnormalities in the lower limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an irregular mass in the right arch of the 12th thoracic vertebra, extending through the intervertebral foramen and into surrounding soft tissue, the maximum diameter of the whole mass being 78 mm. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt nuclear atypia and psammomatous calcification that were positive for PAX8, estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical testing, and of a P53 non-mutational pattern. On clinicopathologic review, the previous 13- × 11- × 9-cm ovarian tumor was an intracystic and exophytic papillary growth without surface involvement; it had ruptured intraoperatively. Microscopically there was serous epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive foci or micropapillary components. The tumor was confined to the right ovary with no peritoneal implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations according to polymerase chain reaction using formalin-fixed paraffin-embedded tissues. We concluded that, after a 13-year disease-free interval, the paraspinal lesion was bone metastasis of low-grade carcinoma originating from the ovarian SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by administration of paclitaxel and carboplatin plus bevacizumab and remains alive 168 months after the initial surgery. Conclusions Pathologists and radiologists should not exclude late recurrence of ovarian SBT/APST when bone metastases are suspected, even when neither peritoneal nor lymph node involvement are detected. Long-term surveillance of women with ovarian serous tumors with no invasive features is recommended.

Objective: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan. Methods: We enrolled 378 healthcare workers (255 women and 123 men) whose Ab titers were analyzed 3 and 6 months after the second dose in our previous study and whose characteristics and adverse effects were collected previously by using a structured self-report questionnaire. Results: The workers’ median age was 44 years. Although injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first dose. Multivariate analysis showed that fever was significantly correlated with female participants for the second dose (odds ratio (OR), 2.139; 95% confidence interval (95% CI), 1.185–3.859), older age for the first dose (OR, 0.962; 95% CI, 0.931–0.994) and second dose (OR, 0.957; 95% CI, 0.936–0.979), and dyslipidemia for the first dose (OR, 8.750; 95% CI, 1.814–42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with a fever than in those without a fever after the first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were, respectively, 21.7% and 19.3% higher in the group in which an anti-inflammatory agent was used than in the group without the use of an anti-inflammatory agent. Conclusion: Participants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects.

Objective: We aimed to determine antibody titers at six months and their percentage change from three to six months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) and to explore clinical variables associated with titers in Japan. Methods: We enrolled 365 healthcare workers (250 women, 115 men) whose three-month antibody titers were analyzed in our previous study and whose blood samples were collected 183 ± 15 days after the second dose. Participant characteristics, collected previously, were used. The relationships of these factors with antibody titers at six months and percentage changes in antibody titers from three to six months were analyzed. Results: Median age was 44 years. Median antibody titer at six months was 539 U/mL. Older participants had significantly lower antibody titers (20s, 752 U/mL; 60s–70s, 365 U/mL). In age-adjusted analysis, smoking was the only factor associated with lower antibody titers. Median percentage change in antibody titers from three to six months was −29.4%. The only factor significantly associated with the percentage change in Ab titers was not age or smoking, but sex (women, −31.6%; men, −25.1%). Conclusion: The most important factors associated with lower antibody titers at six months were age and smoking, as at three months, probably reflecting their effect on peak antibody titers. However, the only factor significantly associated with the attenuation in Ab titers from three to six months was sex, which reduced the sex difference seen during the first three months. Antibody titers may be affected by different factors at different time points.

We evaluated isolates obtained from children with Mycoplasma pneumoniae infection throughout Japan during 2008–2015. The highest prevalence of macrolide-resistant M. pneumoniae was 81.6% in 2012, followed by 59.3% in 2014 and 43.6% in 2015. The prevalence of macrolide-resistant M. pneumoniae among children in Japan has decreased.

In this study, to prepare the fraction containing multifunctional cationic peptides, we first hydrolyzed rice bran protein (RBP) with pepsin. We separated the enzymatic hydrolysate of RBP into 20 fractions containing peptides with different isoelectric point (pI) values by ampholyte-free isoelectric focusing (autofocusing). Subsequently, we examined the antimicrobial activity of each fraction against four pathogens. In addition, we purified the cationic peptides from fractions exhibiting antimicrobial activity by reversed-phase high-performance liquid chromatography and identified them by matrix-assisted laser/desorption ionization–time-of-flight mass spectroscopy. Of five cationic peptides identified, we chemically synthesized three peptides with high pI values and evaluated their multiple functions, including antimicrobial, lipopolysaccharide-neutralizing and angiogenic activities. Our results demonstrated that the three identified cationic peptides exhibited multiple functions with little or no haemolytic activity. Fractions containing cationic peptides obtained from RBP hydrolysate have the potential to be used as dietary supplements and functional ingredients in food products.

Abstract Background Fibrin clot membranes prepared from advanced platelet-rich fibrin (A-PRF) or concentrated growth factors (CGF), despite their relatively rapid biodegradability, have been used as bioactive barrier membranes for alveolar bone tissue regeneration. As the membranes degrade, it is thought that the growth factors are gradually released. However, the mechanical and degradable properties of these membranes have not well been characterized. The purpose of this study was to mechanically and chemically characterize these membranes. Methods A-PRF and CGF clots were prepared from blood samples collected from non-smoking, healthy donors and were compressed to form 1-mm-thick membranes. Platelet-poor plasma-derived fibrin (PPTF) clots were prepared by adding bovine thrombin to platelet-poor plasma. A tensile test was performed at the speed of 1 mm/min. Morphology of the fibrin fibers was examined by SEM. A digestion test was performed in PBS containing trypsin and EDTA. Results In the tensile test, statistical difference was not observed in Young’s modulus, strain at break, or maximum stress between A-PRF and CGF. In strain at break, PPTF was significantly weaker than CGF. Likewise, fibrin fiber thickness and crosslink density of PPTF were less than those of other membranes, and PPTF degraded faster than others. Conclusions Although the centrifugal conditions are different, A-PRF and CGF are prepared by essentially identical mechanisms. Therefore, it is conceivable that both membranes have similar mechanical and chemical properties. Only PPTF, which was prepared by a different mechanism, was characterized as mechanically weaker and enzymatically more degradable.

Nanoparticle-assembled hydroxyapatite (HA) hollow microspheres have a high surface area and are convenient to handle, owing to their characteristic structure. In this study we characterized the protein adsorption of HA hollow microspheres prepared from CaCl2 and K2HPO4 by a water-in-oil-in-water (W/O/W) emulsion method assisted by two surfactants: Span 80 and Tween 20. The HA hollow microspheres adsorbed bovine serum albumin, bovine γ-globulin, equine skeletal muscle myoglobin, and chicken egg white lysozyme in 10 mM sodium phosphate buffer (pH 6.8) in a Langmuir-type adsorption and desorbed the proteins in 800 mM sodium phosphate buffer (pH 6.8). The maximum adsorbed amounts of the HA hollow microspheres were 7.5–9.0 times higher than those of the microrods with a similar size range. The composite membranes of the HA microspheres and the poly(l-lactic acid) (PLLA) microporous membranes exhibited a high adsorption capacity for γ-globulin.

Objective: We aimed to determine antibody (Ab) titres 3 months after the second dose of the BNT162b2 coronavirus disease-2019 (COVID-19) vaccine and to explore clinical variables predicting these titres in Japan. Methods: We enrolled 378 healthcare workers (255 women, 123 men) whose blood samples were collected 91 ± 15 days after the second of two inoculations of the BNT162b2 COVID-19 mRNA vaccine (Pfizer/BioNTech) given 3 weeks apart. Medical histories and demographic characteristics were recorded using a structured self-reported questionnaire. The relationships between Ab titres and these factors were analysed. Results: Median age (interquartile range (IQR)) of the participants was 44 (32–54) years. Median Ab titre (IQR) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen was 764 (423–1140) U/mL. Older participants had significantly lower Ab titres; median (IQR) Ab titres were 942 (675–1390) and 1095 (741–1613) U/mL in men and women in their 20s, respectively, but 490 (297–571) and 519 (285–761) U/mL in men and women in their 60–70s, respectively. In the age-adjusted analysis, the only risk factors for lower Ab titres were male sex and smoking. However, the sex difference may have arisen from the sex difference in smoking rate. Moreover, Ab titres were significantly lower in current smokers than in ex-smokers. Conclusions: The most important factors associated with low Ab titres were age and smoking habit. In particular, current smoking status caused lower Ab titres, and smoking cessation before vaccination may improve the individual efficacy of the BNT162b2 vaccine.

Background: Rotavirus vaccines were introduced in Japan in November 2011. We evaluated the subsequent reduction of the health-care burden of rotavirus gastroenteritis. Methods: We conducted active surveillance for rotavirus gastroenteritis among children under 5 years old before and after the vaccine introduction. We surveyed hospitalization rates for rotavirus gastroenteritis in children in Tsu City, Mie Prefecture, Japan, from 2007 to 2015 and surveyed the number of outpatient visits at a Tsu City clinic from 2010 to 2015. Stool samples were obtained for rotavirus testing and genotype investigation. We assessed rotavirus vaccine coverage for infants living in Tsu City. Results: In the pre-vaccine years (2007-2011), hospitalization rates for rotavirus gastroenteritis in children under 5 years old were 5.5, 4.3, 3.1 and 3.9 cases per 1000 person-years, respectively. In the post-vaccine years (2011-2015), the rates were 3.0, 3.5, 0.8 and 0.6 cases per 1000 person-years, respectively. The hospitalization rate decreased significantly in the 2013-2014 and 2014-2015 seasons compared to the average of the seasons before vaccine introduction (p < 0.0001). In one pre-vaccine year (2010-2011), the number of outpatient visits due to the rotavirus infection was 66. In the post-vaccine years (2011-2015), the numbers for each season was 23, 23, 7 and 5, respectively. The most dominant rotavirus genotype shifted from G3P[8] to G1P[8] and to G2P[4]. The coverage of one dose of rotavirus vaccine in Tsu City was 56.5% in 2014. Conclusion: After the vaccine introduction, the hospitalization rates and outpatient visits for rotavirus gastroenteritis greatly decreased.

Platelet-rich fibrin (PRF) clots have been used in regenerative dentistry most often, with the assumption that growth factor levels are concentrated in proportion to the platelet concentration. Platelet counts in PRF are generally determined indirectly by platelet counting in other liquid fractions. This study shows a method for direct estimation of platelet counts in PRF. To validate this method by determination of the recovery rate, whole-blood samples were obtained with an anticoagulant from healthy donors, and platelet-rich plasma (PRP) fractions were clotted with CaCl2 by centrifugation and digested with tissue-plasminogen activator. Platelet counts were estimated before clotting and after digestion using an automatic hemocytometer. The method was then tested on PRF clots. The quality of platelets was examined by scanning electron microscopy and flow cytometry. In PRP-derived fibrin matrices, the recovery rate of platelets and white blood cells was 91.6 and 74.6%, respectively, after 24 h of digestion. In PRF clots associated with small and large red thrombi, platelet counts were 92.6 and 67.2% of the respective total platelet counts. These findings suggest that our direct method is sufficient for estimating the number of platelets trapped in an insoluble fibrin matrix and for determining that platelets are distributed in PRF clots and red thrombi roughly in proportion to their individual volumes. Therefore, we propose this direct digestion method for more accurate estimation of platelet counts in most types of platelet-enriched fibrin matrix.